Biopolymers, including deoxyribonucleic acid (“DNA”), ribonucleic acid (“RNA”), proteins, polysaccharides, and more complex biopolymers together form the chemical and structural framework for living organisms. Biopolymers serve as a repository for genetic information, catalyze myriad different chemical reactions within organisms, provide many different types of intracellular and intercellular information transmission and communication within organisms, and provide the structural components for cells, organs, and organisms.
During the past century, great strides have been made understanding and learning to manipulate the molecular and cellular biochemical machinery of living organisms. Once the chemical identities and structures of biopolymers were discovered and elaborated, researchers began to chemically synthesize biopolymers and biopolymer fragments to use as tools for research as well as for various types of manufacturing processes. For example, synthesis of oligonucleotides, short DNA and RNA biopolymers having lengths of up to approximately 200 monomer units, provides oligonucleotides of specific sequences that are used to initiate enzyme-catalyzed transcription of DNA, as probes in microarrays and other analytical instruments, for manipulating and controlling gene expression in bacteria and other organisms, and for many other purposes. Similarly, synthesis of peptides, short polymers of amino-acids subunits, provides peptide pharmaceuticals, probes, catalysts, and other useful peptide-based products.
Automated-biopolymer-synthesis systems have been commercially available for many years. Many automated-biopolymer-synthesis systems employ solid substrates, such as polystyrene beads, to which nascent biopolymers are covalently bound and grown by repeating a cycle of monomer-addition reaction steps. The solid substrate allows the reagents used during a reaction step to be easily rinsed from the nascent biopolymers and solid substrate to prepare for a subsequent reaction step. Current automated-biopolymer-synthesis systems generally produce yields of 10, 100, or more nanomoles of each particular biopolymer. However, many of the more recent applications for oligonucleotides and other biopolymers use far smaller amounts of each particular oligonucleotide or other biopolymer, often in the 1 to 100 picomolar range. Many of the currently available automated-oligonucleotide-synthesis systems do not provide economical production of the small amounts of particular oligonucleotides needed for many of the more recent applications. Overproduction of oligonucleotides is expensive, because the monomers and reagents used during the synthetic processes are expensive and used in proportion to molar amounts of product oligonucleotides, and the synthetic steps employ hazardous and toxic reagents that inevitably end up in a waste stream that is expensive to monitor and dispose of.
Because of the disparities between the current demand for many different particular oligonucleotides and other biopolymers in very small amounts, and the comparatively large amounts of oligonucleotides and other biopolymers produced by currently-available automated-biopolymer-synthesis systems, researchers and developers, manufacturers, biopolymer suppliers, and others continue to seek new types of systems and methods for cost-effective automated synthesis of small amounts of particular oligonucleotides and other biopolymers. In certain cases, processing steps and components of currently available, relatively large-volume automated-biopolymer-synthesis systems can be scaled down for developing small-volume systems. However, in certain cases, processes and components of the currently-available large-volume automated-biopolymer-synthesis systems do not scale down effectively for incorporation into small-volume systems. As a result, researchers, designers, and manufacturers continue to seek new processes, components, and subcomponents to replace those processes, components, and subcomponents of currently available large-volume automated-biopolymer-synthesis systems that cannot be scaled down for incorporation into small-volume systems.